This project is designed to apply quantitative systems which measure normal tissue damage and tumor response in the mouse to the evaluation of factors and agents which modify radiation response in ways which may be favorable to the therapeutic ratio. Fractionation, hyperthermia, cancer chemotherapeutic agents and heavy particle irradiation have the potential for increasing tumor response, a lesser increase in normal tumor response, and thus an increase in therapeutic ratio. Normal tissue endpoints are measured in the brain, lung, esophagus, kidney, small intestine, skin and bone marrow; tumor response is measured in the EMT6 carcinoma assayed as a solid tumor, as small metastases and in vitro. Hyperthermia is being generated by a specially designed microwave apparatus and irradiation chamber for segmental heating of mice. Drugs being investigated include Adriamycin, Actinomycin, BCNU, Cyclophosphamide, and Bleomycin. High LET radiations under investigation include 15 MeV neutrons, helium ions, and neon ions, as well as carbon and argon.